Tivdak (tisotumab vedotin-tftv)

P3, N=502, Completed, Seagen, a wholly owned subsidiary of Pfizer | Active, not recruiting --> Completed | Trial completion date: May 2026 --> Jan 2026

Currently, three ADCs have received Food and Drug Administration (FDA) approval for use in gynecologic malignancies: mirvetuximab soravtansine, tisotumab vedotin, and trastuzumab deruxtecan. Furthermore, the inherent complexities of these drugs and their mechanisms of action underscore the need for further research into the relevance of biomarkers, methods of therapy resistance, and the potential for re-utilization of payloads and targets later in the disease course. This review focuses on the mechanisms of action of ADCs, their developmental trajectory, successes in gynecologic cancers, emerging areas of investigation, the prospective landscape, and current challenges in the field.

The analysis focuses on treatments that have demonstrated clinical benefit in advanced or recurrent disease, including pembrolizumab, dostarlimab, tisotumab vedotin, and mirvetuximab soravtansine. Their growing integration into clinical practice has reshaped therapeutic approaches, while ongoing research continues to refine optimal combinations, address resistance, and enhance biomarker-guided selection. Future developments are expected to unite immunologic, genomic, and computational strategies to achieve personalized and durable outcomes for patients with gynecologic malignancies.

P=N/A, N=20, Not yet recruiting, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; Sun Yat-sen Memorial Hospital, Sun Yat-sen University

For locally advanced disease, KEYNOTE-A18 establishes pembrolizumab plus chemoradiation as a new curative standard, while INTERLACE underscores the benefit of induction chemotherapy. In the metastatic setting, survival outcomes have improved with the integration of checkpoint inhibitors (KEYNOTE-826, BEATcc, EMPOWER-Cervical 1), vascular-targeted therapies, and antibody-drug conjugates, including tisotumab vedotin and emerging HER2 and TROP-2-directed agents...Future directions include neoadjuvant checkpoint inhibition, PARP-IO combinations, HER3-directed ADCs, DDR-targeted radiosensitizers, HPV-specific cellular therapies, and AI-integrated precision medicine. Collectively, these advances are reshaping cervical cancer care toward biologically individualized, globally implementable strategies capable of accelerating WHO elimination targets.

P2, N=352, Active, not recruiting, Seagen, a wholly owned subsidiary of Pfizer | Trial completion date: Sep 2026 --> Mar 2027

The simultaneous or sequential presentation of cervical and breast cancer is rare, especially under systemic treatment. The patient's cervical cancer was aggressive, and the subsequent metachronous breast cancer highlights the complex, multifactorial nature of carcinogenesis. The development of a second primary malignancy while a patient is receiving treatment for a metastatic condition is a critical clinical scenario, necessitating individualized treatment strategies, as optimal management remains unclear due to the rarity of such cases.

Particularly, the combination of platinum-based chemotherapy and pembrolizumab, with or without bevacizumab, has been established as the new standard treatment for primary metastatic or recurrent PD-L1 positive high-risk cervical cancer. In locally advanced cervical cancer, two new treatment escalation regimens-neoadjuvant chemotherapy and adjuvant CPI therapy-have been evaluated in addition to chemoradiation. Furthermore, antibody-drug conjugates, such as tisotumab-vedotin, represent a promising future therapeutic option for recurrent cervical cancer.

P3, N=686, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Oct 2028 --> Jun 2028 | Trial primary completion date: Oct 2028 --> Jun 2028

These developments reflect a shift toward precision medicine that integrates immunotherapy, antiangiogenic, and targeted agents; however, challenges persist in optimizing treatment sequences, overcoming resistance, and identifying biomarkers to personalize care. Addressing global disparities in prevention and treatment access remains essential to achieving the WHO's goal of eliminating cervical cancer by 2030.

P2, N=352, Active, not recruiting, Seagen, a wholly owned subsidiary of Pfizer | Trial primary completion date: Sep 2025 --> Jan 2026

For cervical, vulvar and vaginal cancers specifically, trastuzumab deruxtecan and tisotumab vedotin could be important therapeutic options in the right context. In this review, we describe the molecular features of different cervical, vulvar and vaginal cancer types, current genomically-matched therapies being investigated and discuss treatment strategies with future potential.